Abstract

BackgroundAvascular necrosis (AVN) is a major cause of morbidity and loss of quality of life in systemic lupus erythematosus (SLE) patients. AVN is often diagnosed at advanced stages and treatment options are limited.ObjectivesTo identify the differences of demographic, clinical, and serological factors in SLE patients with and without AVN, and to investigate associated risk factors of AVN in patients with SLE.MethodsIn this single-centre retrospective cohort study, we included 533 SLE patients [88.6% female, mean (standard deviation, (SD)) age at diagnosis 34.6 (14.3) years] who fulfilled SLICC 2012 classification criteria. AVN diagnosis was confirmed by radiological imaging techniques in symptomatic patients. To investigate the correlation between maximum daily steroid dose and AVN development, we divided our patients into four groups according to the highest dose of prednisolone used for a month or longer during their follow-up (Group 1: 0-19mg/day, Group 2: 20-39mg/day, Group 3: 40-59mg/day, Group 4:≥60mg/day). Pulse steroid administration was also recorded. Multivariable logistic regression analyses were performed to demonstrate the associated factors with AVN. Clinical parameters found to be related to AVN development in univariable analyses were analyzed both in the sex- and age-adjusted model, and the model including sex, age, time to AVN or last follow-up, immunosuppressive therapy, and steroid dosages (multivariable model). To determine the relation of different steroid groups and pulse steroids with AVN, odds ratios (OR) were calculated in the sex- and age-adjusted model and multivariable model.ResultsAfter a median disease duration of 9.1 years, AVN was detected in 46 (8.6%) patients. There were 85 AVN sites involved, the hips being the most commonly affected (71.7%) (Figure 1). The mean age at SLE diagnosis was significantly younger in the AVN group (mean (SD) 26.8 (11.7) vs. 35.3 (11.4), p<0.001). Fever (21.6% vs. 10.9%), malar rash (52.2% vs. 36.3%), serositis (26.1% vs. 14.6%), renal involvement (65.2% vs. 35.1%) and hemolytic anemia (32.6% vs. 19.3%) were found more frequently in the AVN group compared to non-AVN group, respectively (p<0.05). In the multivariable logistic regression analyses, malar rash was found to be the only clinical feature associated with AVN (OR 2.01, 95% confidence interval (CI) 1.02-3.97). The steroids had an association with AVN development in a dose-dependent manner (Table 1). Pulse steroids did not increase the risk of AVN (Table 1).Table 1.Factors associated with avascular necrosis.Association between maximum daily steroid dose and AVNOR Crude(95% CI)OR Age-sex adjusted(95% CI)OR fully adjusted*(95% CI)0-19 mg/day(reference group)1.00 (reference group)20-39 mg/day7.22 (1.29-40.31)6.63 (1.18-32.28)5.86 (1.00-34.37)40-59 mg/day14.08 (3.02-65.63)10.69 (2.25-50.75)8.79 (1.77-43.61)≥60 mg/day31.50 (7.39-134.19)26.03 (6.02-112.59)13.93 (3.07-63.16)Association between pulse steroid treatment and AVNOR Crude(95% CI)OR Age-sex adjusted(95% CI)OR fully adjusted*(95% CI)No pulse steroids1.00 (reference group)Pulse steroids6.29 (3.35-11.81)4.86 (2.53-9.37)1.51 (0.69-3.32)*In addition to the age at SLE diagnosis and sex, immunosuppressant use, and follow-up duration were also added to the final model.Figure 1.Magnetic resonance imaging of avascular necrosis of bilateral femoral heads in a patient with SLE.ConclusionHigh-dose daily steroid use was associated with an increased risk of AVN in SLE patients. Therefore, to prevent AVN in patients with SLE, the aim should be minimizing the dosage and duration of steroid use as much as possible. Furthermore, we showed that malar rash independently increased the risk of AVN development. Further research is required to explain this finding.

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